scholarly journals Preoperative hyperlactatemia and early mortality after liver transplantation: selection of important variables using random forest survival analysis

Author(s):  
Yuseon Cheong ◽  
Sangho Lee ◽  
Do-Kyeong Lee ◽  
Kyoung-Sun Kim ◽  
Bo-Hyun Sang ◽  
...  

Background: Generally, lactate levels > 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is often defined as lactate > 4 mmol/L. Although hyperlactatemia is common finding in liver transplant (LT) candidates, association between lactate and organ failures with Acute-on-chronic Liver Failure (ACLF) is poorly studied. We searched the important variables for pre-LT hyperlactatemia and examined the impact of preoperative hyperlactatemia on early mortality after LT. Methods: A total of 2,002 patients from LT registry between January 2008 and February 2019 were analyzed. Six organ failures (liver, kidney, brain, coagulation, circulation, and lung) were defined by criteria of EASL-CLIF ACLF Consortium. Variable importance of preoperative hyperlactatemia was examined by machine learning using random survival forest (RSF). Kaplan-Meier Survival curve analysis was performed to assess 90-day mortality.Results: Median lactate level was 1.9 mmol/L (interquartile range: 1.4, 2.4 mmol/L) and 107 (5.3%) patients showed > 4.0 mmol/L. RSF analysis revealed that the four most important variables for hyperlactatemia were MELD score, circulatory failure, hemoglobin, and respiratory failure. The 30-day and 90-day mortality rates were 2.7% and 5.1%, whereas patients with lactate > 4.0 mmol/L showed increased rate of 15.0% and 19.6%, respectively. Conclusion: About 50% and 5% of LT candidates showed pre-LT hyperlactatemia of > 2.0 mmol/L and > 4.0 mmol/L, respectively. Pre-LT lactate > 4.0 mmol/L was associated with increased early post-LT mortality. Our results suggest that future study of correcting modifiable risk factors may play a role in preventing hyperlactatemia and lowering early mortality after LT.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 682-682
Author(s):  
Brian Cox ◽  
Nicholas Manguso ◽  
Humair Quadri ◽  
Jessica Crystal ◽  
Katelyn Mae Atkins ◽  
...  

682 Background: Lymph node (LN) metastases affect overall survival (OS) in pancreatic cancer (PC). However, a LN sampling threshold does not exist. We examined the impact of nodal sampling on overall survival (OS). Methods: Patients with Stage I-III PC ≥55 years old who underwent curative resection from 2004-2016 were identified from the National Cancer Database (NCDB). After adjusting for age, gender, grade, stage, and Charlson-Deyo score, multiple binomial logistic regression analyses assessed the impact of the LN ratio (LNR) on OS. LNR was defined as the number of positive LN over the number of LN examined. Regression analyses, a Cox-Regression, and a Kaplan-Meier survival curve assessed how many LN should be sampled. Results: A total of 13,673 patients, median age 69 years (55-90), were included. Most were Caucasian (86.6%) males with Charlson-Deyo scores ≤ 1 (90.3%) and moderately to poorly differentiated PC (90.1%). Median number of LN examined was 15 (1-75) with a median of 1 positive LN (0-35). As expected, increased number of positive LNs was associated with reduced OS, p < 0.001. After data normalization, an increasing LNR was associated with a 12-fold likelihood of death [OR: 11.9, p < 0.001 (CI 6.0, 23.7)]. Subsequent regression models established evaluation of ≥ 16 LNs as the greatest predictor of OS. A regression model evaluating < or ≥ 16 lymph nodes was performed to ascertain the effects of age, gender, ethnicity, grade, stage, and LN examined on OS. The logistic regression model correctly classified 74.5% of cases with a specificity of 99.6% (p < 0.001). Examination of < 16 LN, Caucasian race, grade, stage, and higher Charlson-Deyo scores were significantly associated with decreased OS. If ≥ 16 LNs were examined, patients had a 1.5-fold likelihood of better OS, p < 0.001 (CI 1.4, 1.6). An adjusted Cox Regression showed increased HR of 1.2, p < 0.001 (CI 1.1, 1.2) and an unadjusted Kaplan Meier survival curve predicted ≥ 16 LN examined are associated with an increase in OS of 2.8 months [log-rank: 32.0, p < 0.001]. Conclusions: Patients undergoing curative intent resection for PC should have adequate nodal sampling. Stratification of patients by LNR may provide useful information of OS. Examination of ≥ 16 LNs impacts OS in patients with Stage I-III PC.


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R Marinheiro ◽  
L Parreira ◽  
P Amador ◽  
D Mesquita ◽  
J Farinha ◽  
...  

Abstract Introduction Data suggest inappropriate defibrillator shocks are associated with a higher risk of all-cause mortality, particularly those delivered for atrial fibrillation (AF). However, the impact of inappropriate shocks has not been studied specifically in a population with AF. Aims to determine if AF-triggered inappropriate shocks are associated with long- term mortality in patients with AF and defibrillators implanted for primary prevention. Methods Retrospective single-center study. We analyzed all patients with defibrillators implanted for primary prevention in whom AF was diagnosed until the end of 2017. The cause of inappropriate shocks was evaluated by analysis of the stored intracardiac electrogram. Basal characteristics, cardiovascular risk factors, left ventricle ejection fraction, heart failure etiology (ischemic and non-ischemic), kidney function (creatinine) and medication were evaluated. Death was assessed during the follow-up. Results We studied 177 patients [median age 66 years (IQR 59-71); 82% male], with defibrillators and AF. AF was diagnosed before defibrillator implantation in 131 patients (74%) and after the implantation in the remaining 46 (26%). Inappropriate shocks occurred in 31 patients and 24 (14%) were caused by AF with rapid ventricular response: 13 patients with previously diagnosed AF and 11 with new-onset AF. During a median follow-up of 65 (IQR: 36-104) months, 74 patients died. Multivariate Cox-regression analysis demonstrated inappropriate shocks caused by AF were not independently related with death (adjusted HR 0.53; CI 0.23-1.23, p = 0.14). Kaplan-Meier survival curve demonstrated patients with AF-triggered inappropriate shocks had a better survival comparing to those with AF but without inappropriate shocks (logrank, p = 0.03) (figure). Conclusions In this group of AF patients, inappropriate shocks caused by AF did not increase the risk of death. Instead, these patients had a better survival comparing to those with AF but no shocks, probably due to a re-evaluation of the patient´s status and subsequent closer medical monitoring, strictly control of symptoms and optimization of drug treatment. These results demonstrate that inappropriate shocks are probably not deleterious per si through a direct mechanism. Abstract Figure. Kaplan-Meier survival curve


2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Zhenhua Tan ◽  
Renrui Wan ◽  
Minzhi Chen ◽  
Ping Xie ◽  
Peng Li ◽  
...  

The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. High invasion and metastasis are one of the main causes of death in patients. The selection of reasonable and effective molecular markers to evaluate the prognosis of patients with ICC has important clinical guiding significance. In this study, the expression of Tspan protein in ICC and normal tissues was compared, the correlation between Tspan expression and pathological features of patients was analyzed by the logistic regression model using multivariate analysis, and the relationship between Tspan8 expression and prognosis of ICC patients was analyzed by the Kaplan–Meier survival curve. The results showed that Tspan8 is highly positive in ICC tissues, TNM stage, degree of tumor differentiation, lymph node metastasis, and Tspan8 protein expression were independently correlated, and the overexpression of Tspan was associated with the prognosis of ICC invasion and metastasis. This provides a new idea for clinical treatment.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chunxia Zhao ◽  
Yulu Wang ◽  
Famei Tu ◽  
Shuai Zhao ◽  
Xiaoying Ye ◽  
...  

BackgroundSome studies have proven that autophagy and lncRNA play important roles in AML. Several autophagy related lncRNA signatures have been shown to affect the survival of patients in some other cancers. However, the role of autophagy related lncRNA in AML has not been explored yet. Hence, this study aims to find an autophagy related lncRNA signature that can affect survival for AML patients.MethodA Pearson correlation analysis, a Kaplan–Meier survival curve, a univariate cox regression, and a multivariate cox regression were performed to establish an autophagy related lncRNA signature. A univariate cox regression, a multivariate cox regression, a Kaplan–Meier survival curve, and a ROC curve were applied to confirm if the signature is an independent prognosis for AML patients. The relationship between the signature and the clinical features was explored by using a T test. Gene Set Enrichment Analysis (GSEA) was used to investigate the potential tumor related pathways.ResultsA four-autophagy related lncRNA (MIR133A1HG, AL359715.1, MIRLET7BHG, and AL356752.1) signature was established. The high risk score based on signature was related to the short survival time of AML patients. The signature was an independent factor for the prognosis for AML patients (HR = 1.684, 95% CI = 1.324–2.142, P &lt; 0.001). The signature was correlated with age, leukocyte numbers, and FAB (M3 or non-M3). The P53, IL6/JAK/STAT3, TNF-α, INF-γ, and IL2/STAT5 pathways might contribute to the differences between the risk groups based on signature in AML.ConclusionThe four autophagy related lncRNAs and their signature might be novel biomarkers for predicting the survival of AML patients. Some biological pathways might be the potential mechanisms of the signature for the survival of AML patients.


2021 ◽  
Author(s):  
Sukyo Lee ◽  
Juhyun Song ◽  
Dae Won Park ◽  
Hyeri Seok ◽  
Jae-hyung Cha ◽  
...  

Abstract Background: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. Early diagnosis of sepsis is challenging due to unknown sources of infection, and mortality prediction is usually complex. We aimed to investigate the clinical value of presepsin for discriminating sepsis from non-infectious organ failure and predicting mortality among sepsis patients in the emergency department (ED).Methods: This prospective observational study included 420 patients divided into three groups according to the Sepsis-3 definitions: non-infectious organ failure (n=142), sepsis (n=141), and septic shock (n=137). Blood samples for biomarker measurement of presepsin, procalcitonin, and C-reactive protein were drawn in the ED and biomarker levels were compared between the groups. Optimal cut-off values for presepsin to discriminate between the three clinical diagnoses were evaluated using receiver operating characteristic (ROC) curve analysis. We also performed ROC curve analysis for each biomarker as a predictor of mortality. After excluding non-infectious organ failure, we extracted the optimal cut-off value of presepsin to predict mortality associated with sepsis and septic shock and performed Kaplan–Meier survival curve analysis according to the cut-off value.Results: Presepsin levels (median [IQR]) were significantly higher in sepsis than in non-infectious organ failure (792 [450–1273] vs. 286 [170–417], p <0.001) and significantly higher in septic shock than in sepsis (1287 [589–2365] vs. 792 [450–1273], p=0.002). The optimal cut-off value for presepsin to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (sensitivity, 70.1; specificity, 89.4; AUC, 0.877; p <0.001) and to discriminate between sepsis and septic shock was 1285 pg/mL (sensitivity, 50.4; specificity, 76.6; AUC, 0.618; p <0.001). The optimal cut-off value for presepsin for predicting 30-day mortality was 821 pg/mL (sensitivity, 68.9; specificity, 50.5; AUC, 0.605; p=0.005) in patients with sepsis and septic shock. Kaplan-Meier survival curve analysis showed that patients with higher presepsin levels (≥821 pg/mL) had significantly higher mortality than patients with lower presepsin levels (<821 pg/mL) (log-rank test; p=0.004). Conclusions: Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and septic shock from sepsis. Presepsin levels could help clinicians predict mortality in patients with sepsis and septic shock.


2018 ◽  
Vol 47 (1-3) ◽  
pp. 101-108 ◽  
Author(s):  
Renhua Lu ◽  
Chenqi Xu ◽  
Yan Li ◽  
Ling Yu ◽  
Xinghua Shao ◽  
...  

Objective: To investigate the incidence and the prognosis of cognitive impairment (CI) and to find out the risk factors associated with the outcome in maintenance haemodialysis (MHD) patients. Methods: Enrolled the patients who met the criteria as below: MHD (≥3 months) patients before July 2014, ≥18 years old and could carry on the cognitive function test (Montreal Cognitive Assessment [MoCA]). All enrolled patients were divided into 2 groups: CI group (MoCA < 26) and non-CI group (MoCA ≥26). All patients were followed up for 36 months. The incidence, demography data, medical history, haemodialysis data, laboratory examination and prognosis of CI in haemodialysis patients were prospectively compared and analyzed. Multivariate logistic regression analysis was used to investigate the risk factors of CI. Kaplan-Meier survival curve was used for survival analysis. Results: In the present study, 219 patients were enrolled. The ratio of male to female was 1.46: 1. Age was 60.07 ± 12.44 and dialysis vintage was 100.79 ± 70.23 months. One hundred thirteen patients’ MoCA scores were lower than 26 were divided into CI group. Education status (OR 3.428), post-dialysis diastolic pressure (OR 2.234) and spKt/V (OR 1.982) were independent risk factors for CI in MHD patients. During the follow-up period, 15 patients died (13.2%) in the CI group and 5 died (4.72%) in the non-CI group (p < 0.05). The Kaplan-Meier survival curve analysis showed that the survival rate of patients with CI was lower than that of non-CI group in MHD patients during 3 years follow-up (p = 0.046). Conclusion: CI is one of the most common complications in MHD patients. The mortality is high in patients who had CI. Education status, post-dialysis diastolic pressure and spKt/V are independent risk factors for CI in MHD patients.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi79-vi80
Author(s):  
Yesh Banasavadi ◽  
Sriya Namagiri ◽  
yoshihiro Otani ◽  
Shilpa Thammegowda ◽  
Hannah Sur ◽  
...  

Abstract With limited effective therapeutic strategies, the prognosis for glioblastoma (GBM) is very poor. Our previous study shows that the expression of Protein Arginine Methyltransferase 5 (PRMT5) is upregulated in GBM; its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. MEK inhibitors, including trametinib, are currently under investigation for GBM therapy. In this study, we tested whether inhibition of PRMT5 can enhance the anti-GBM efficacy of trametinib. Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot analysis were conducted. In vivo, PRMT5-intact and -depleted GBMNS were intracranially implanted in NSG mice and treated with trametinib by daily oral gavage, and tumor progression and mice survival rate were analyzed by MRI and Kaplan-Meier survival curve, respectively. Depletion of PRMT5 increased the cytotoxic effect of trametinib in GBMNS. Trametinib treatment increased the activity of ERBB3 and AKT; With PRMT5 knockdown, the activity of both AKT and ERBB3 decreased significantly. But, inhibition of ERBB3 alone failed to block the trametinib-induced AKT activity suggesting that even though PRMT5 regulates the activity of both ERBB3 and AKT, the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib treated GBMNS is because of AKT inhibition alone. In vivo, PRMT5-depletion extended the survival of the tumor-bearing mice that further increased in combination with trametinib treatment. Interestingly, trametinib treatment alone had no survival benefit.


2016 ◽  
Vol 27 (4) ◽  
pp. 452-457 ◽  
Author(s):  
Gabrielle Branco Rauber ◽  
Jussara Karina Bernardon ◽  
Luiz Clovis Cardoso Vieira ◽  
Hamilton Pires Maia ◽  
Françoá Horn ◽  
...  

Abstract The aim of this study was to compare the fatigue resistance of restored teeth with bulk fill composite resin, conventional composite resin with incremental insertion and unprepared sound teeth. Twenty-eight extracted maxillary premolars were selected and divided into 4 groups based on composite resin and insertion technique: control (C), conventional composite resin with incremental insertion (I) and bulk fill composite resin with three (BF3) or single increment (BF1). The restored specimens were submitted to fatigue resistance test with a 5 Hz frequency. An initial application of 5,000 sinusoidal load cycles with a minimum force of 50 N and a maximum force of 200 N was used. Next, were applied stages of 30,000 load cycles with the maximum force increasing gradually: 400, 600, 800, 1000, 1200 and 1400 N. The test was concluded when 185,000 load cycles were achieved or the specimen failed. The fatigue resistance data were recorded for comparison, using the Kaplan-Meier survival curve and analyzed by log-rank test at 0.05 significance. Fractures were classified based on the position of the failure - above or below the cementoenamel junction (CEJ). Statistical analysis of the Kaplan-Meier survival curve and log-rank test showed a significant difference between groups (p=0.001). The fracture analysis demonstrated that only 28.58% of failures were below the CEJ in group C, while for groups I, BF1 and BF3 they were 42.85%, 85.71% and 85.71%, respectively. Teeth restored with composite bulk fill in both techniques present similar fatigue resistance values compared with those restored with a conventional incremental insertion of composite, while the fatigue strength values of unprepared sound teeth were higher. Furthermore, unprepared sound teeth showed a lower percentage of fractures below the CEJ.


2019 ◽  
Vol 6 (1) ◽  
pp. e000343
Author(s):  
Rosana Quintana ◽  
Guillermo Pons-Estel ◽  
Karen Roberts ◽  
Monica Sacnún ◽  
Guillermo Berbotto ◽  
...  

ObjectiveTo compare the clinical, laboratory and outcome features of SLE patients with and without Jaccoud’s arthropathy (JA) from the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort.Methods1480 patients with SLE [(34 centres, 9 Latin American countries with a recent diagnosis (≤2 years)] constitute the GLADEL cohort. JA was defined as reducible deformity of the metacarpophalangeal axis, without radiographic erosions at any time. Within this cohort, a nested case–control study was carried out. Control was matched for age, gender and centre in a 1:3 proportion. The variables included were: sociodemographic, clinical and immunological features, disease activity, damage and mortality. Comparisons were performed with Wilcoxon and χ2 tests for continuous and categorical variables, respectively. ORs and 95% CIs and Kaplan-Meier survival curve were estimated.ResultsOf 1480 patients, 17 (1.1%) JA patients were identified; 16 (94.1%) of them were women, mean age: 31.0 years (SD 12.0). Five (29.4%) patients presented JA at SLE diagnosis and 12 (70.6%) after. The median follow-up time and all disease features were comparable in both groups except for a higher frequency of pneumonitis in the patients with JA [4 (23.5) vs 1 (2.0); p=0.012; (OR: 15.4; 95% CI 1.6 to 149.6)]. The SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage Index and the Kaplan-Meier survival curve were similar in both groups.ConclusionJA may tend to appear early in the course of SLE; it seems not to have an impact on disease activity, damage accrual or in survival.


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